A H-1-NMR STUDY OF THE DNA-BINDING OF RUTHENIUM(II) POLYPYRIDYL COMPLEXES

H-1 NMR spectroscopy was used to study the oligonucleotide binding of the a enantiomers of [Ru(phen)(2)L](2+) where the bidentate ligand L i s 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) or yrido-[3,2-a:2',3'-c](6,7,8,9-tetrahydro)phenazine (dpqC). The dat a from one- and two-dimensional NMR experiments of the oligonucleotide -metal complex binding suggest that all three ruthenium(II) polypyridy l complexes bind in the DNA minor groove. While a minimally intercalat ed oligonucleotide binding mode may be proposed for Delta-[Ru(phen)(3) ](2+), the NMR data clearly indicate that Delta-[Ru(phen)(2)dpq](2+) b inds the hexanucleotide d(GTCGAC)(2) by intercalation, of the dpq liga nd, from the minor groove. This demonstrates that metallointercalators can intercalate from the DNA minor groove. Molecular modeling of the metal complex in the intercalation site suggests that Delta-[Ru(phen)( 2)dpq](2+) binds in a ''head-on'' fashion with the phenanthroline ring s in the minor groove and the dpq ligand inserted into the nucleotide base stack. NOESY experiments of the binding of Delta-[Ru(phen)(2)dpq] (2+) with d(GTCGAC)(2) and d(TCGGGATCCCGA)(2) suggest that intercalati on from the minor groove is favored at purine-purine/pyrimidine-pyrimi dine sequences for this complex. The syntheses of Delta-[Ru(phen)(2)dp q](2+) and Delta-[Ru(phen)(2)dpqC](2+) are reported along with crystal structure of [Ru(phen)(2)dpq](PF6)(2) (monoclinic crystal system, spa ce group P2(1)/c, Z = 4, a = 9.483(2) Angstrom, b = 33.374(6) Angstrom , c = 12.900(3) Angstrom, beta = 110.05(2)degrees, V= 3835(2) Angstrom (3)).